Evidence has demonstrated that pancreatic digestive enzymes, once secreted by the pancreas into the lumen of the intestine, can be absorbed intact from the gut, transported back to the pancreas, and resecreted by the pancreas. The object of this study is to investigate the extent, utility and control of this system and the characteristics of the molecular mechanisms mediating the necessary transcellular movement of intact proteins. Investigation into the extent and purpose of recirculation must explore certain key questions: (1) is circulation solely a trace effect producing a negative feedback control system governing secretion and/or synthesis of enzyme from the pancreas? (2) in what section of the gut does most reabsorption occur and what is the nature of the reabsorptive process? (3) are only proenzymes circulated or does there exist some mechanism for inactivating enzyme? (4) does hormonal and neuronal stimulation control the circulatory pattern? The investigation will be performed using rabbits because of the unique advantages offered by this species in the in-vitro pancreas preparation. Because of the diffuse nature of the rabbit pancreas, this organ can function intact in a bath for many hours under uniformly controlled conditions. This system in conjunction with tissue incubations will provide for studying the isolated pancreas; gut sacs, and intestinal preparations in Ussing Chambers will be utilized for studying the integrated system. Studies will follow radioactive tracer movement and/or bulk movement of an enzyme. The studies outlined may be of importance in determining the fate of the large pool of proteins secreted by the pancreas each day (10-30 grams) and in exploring the mechanisms for intestinal handling of such proteins.